5F1R
The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)
Summary for 5F1R
| Entry DOI | 10.2210/pdb5f1r/pdb |
| Related | 2BEO |
| Descriptor | Listeriolysin regulatory protein, (3~{R})-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid (3 entities in total) |
| Functional Keywords | dna binding protein, prfa, 2-pyridones, virulence |
| Biological source | Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e) |
| Total number of polymer chains | 2 |
| Total formula weight | 55413.69 |
| Authors | Begum, A.,Grundstrom, C.,Good, J.A.D.,Andersson, C.,ALmqvist, F.,Johansson, J.,Sauer, U.H.,Sauer-Eriksson, A.E. (deposition date: 2015-11-30, release date: 2016-03-16, Last modification date: 2024-01-10) |
| Primary citation | Good, J.A.,Andersson, C.,Hansen, S.,Wall, J.,Krishnan, K.S.,Begum, A.,Grundstrom, C.,Niemiec, M.S.,Vaitkevicius, K.,Chorell, E.,Wittung-Stafshede, P.,Sauer, U.H.,Sauer-Eriksson, A.E.,Almqvist, F.,Johansson, J. Attenuating Listeria monocytogenes Virulence by Targeting the Regulatory Protein PrfA. Cell Chem Biol, 23:404-414, 2016 Cited by PubMed Abstract: The transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes cellular uptake by reducing the expression of virulence genes. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA-binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds at two separate sites on the protein: one within a hydrophobic pocket or tunnel, located between the C- and N-terminal domains of PrfA, and the second in the vicinity of the DNA-binding helix-turn-helix motif. At both sites the compound interacts with residues important for PrfA activation and helix-turn-helix formation. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes. PubMed: 26991105DOI: 10.1016/j.chembiol.2016.02.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
Download full validation report
